The capability to develop new anti-cancer agents is essential to the mission of the Cancer Center. The Translational Pharmacology and Early Therapeutic Trials (TPETT) Program accomplishes this by: 1) supporting the preclinical development of anti-cancer agents identified by DF/HCC investigators, and 2) defining the toxicity, pharmacokinetics and pharmacodynamics of new agents from the Center, NCI and pharmaceutical companies In Early Phase trials. The overall objective of the TPETT Program is, thus, to foster a coordinated effort: through which promising new leads and agents are developed for evaluation in Early Phase clinical trials and then in Phase 11 in conjunction with the Clinical-based Programs. The Program facilitates the development of anti-cancer agents by combining basic science and clinical resources at the DFCI, MGH, BWH, BIDMC and CHB. Its Specific Aims are to: 1) strengthen and expand preclinical drug discovery and development efforts; 2) perform translational studies to identify responsive subsets of tumors and confirm mechanism of action in the clinic; 3) conduct Phase I, l-ll pharmacokinetic/pharmacodynamic trials of new anti-cancer agents with correlative laboratory and imaging studies to define biological endpoints and mechanisms; and 4) develop biomarkers for drug response, resistance and toxicity. The 49 members of this program represent six DF/HCC institutions and eight departments of HMS. In 2009, members received $10.4 million (total costs) in cancer-relevant funding, including $2.7 million from NCI and $370,000 from other peer-reviewed sponsors. In addition, members published 500 papers during the project period (2006 to 2010), of which 12.4% were intra-programmatic, 50% were inter-programmatic, and 25.4% were inter-institutional. The Program has been continuously funded as a CCSG Program for ten years. At the time of the last competitive renewal in 2005, the Program received Excellent merit.